Organ Distribution of 3-Hydroxy-3-methylglutaric Acid, a Potential Anticholesterolemic Agent

Abstract

The distribution of radioactivity after oral administration of 3-hydroxy-3-[3-14C]methylglutaric acid has been studied by whole-body autoradiography in the mouse. The compound (a potential anticholesterolemic agent) was promptly and almost completely absorbed. Relatively high and persistent levels of radioactivity were seen in organs responsible for cholesterol synthesis, mainly liver and intestinal wall. Rapid and pronounced uptake of radioactivity was seen in the kidney and the time course of the level of radioactivity indicated that the kidney is not only the main excretory route of 3-hydroxy-3-methylglutaric acid but also represents an important site of distribution of the compound. Detectable uptake of radioactivity, mainly in the first phase, occurred also in the lungs, the salivary glands, the lacrimal glands, the skin, and the brown fat. Results obtained by autoradiography have been checked in part by direct measurement of radioactivity in individual organs and data obtained with the two techniques are in agreement.